Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.

Background Heart failure with preserved ejection fraction (HFPEF) is common and characterized by exercise intolerance and lack of proven effective therapies. Exercise training has been shown to be effective in improving cardiorespiratory fitness (CRF) in patients with systolic heart failure. In this meta-analysis, we aim to evaluate the effects of exercise training on CRF, quality of life and diastolic function in patients with HFPEF. Methods and Results Randomized controlled clinical trials that evaluated the efficacy of exercise training in patients with HFPEF were included in this meta-analysis. Primary outcome of the study was change in CRF (measured as change in peak oxygen uptake). Impact of exercise training on quality of life (estimated using Minnesota living with heart failure score), left ventricular systolic and diastolic function was also assessed. The study included 276 patients that were enrolled in 6 randomized controlled trials. In the pooled data analysis, HFPEF patients undergoing exercise training had significantly improved CRF (L/min) (Mean difference: 2.72; 95% CI: 1.79 to 3.65) and quality of life (Mean difference: −3.97; 95% CI: −7.21 to −0.72) as compared with the control group. However, no significant change was observed in the systolic function [Ejection Fraction – Weighted Mean difference (WMD): 1.26; 95% CI: −0.13% to 2.66%] or diastolic function [E/A - WMD: 0.08; 95% CI:−0.01 to 0.16] with exercise training in HFPEF patients. Conclusions Exercise training in patients with HFPEF is associated with an improvement in CRF and quality of life without significant changes in left ventricular systolic or diastolic function.

Hyperlipidemia is a well-established risk factor for developing cardiovascular disease (CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia. Recently the Food and Drug Administration approved two novel medications for low-density lipoprotein (LDL)-cholesterol reduction: Evolocumab and Alirocumab. These agents target and inactivate proprotein convertase subtilsin-kexin type 9 (PCSK9), a hepatic protease that attaches and internalizes LDL receptors into lysosomes hence promoting their destruction. By preventing LDL receptor destruction, LDL-C levels can be lowered 50%-60% above that achieved by statin therapy alone. This review explores PCSK-9 biology and the mechanisms available to alter it; clinical trials targeting PCSK9 activity, and the current state of clinically available inhibitors of PCSK9.

IntroductionThe aim of the study was to investigate predictors of mortality in patients hospitalized with hyperkalemia.Material and methodsData among hospitalized patients with hyperkalemia (serum potassium ≥ 5.1 mEq/l) were collected. Patients with end-stage renal disease on dialysis were excluded.ResultsOf 15,608 hospitalizations, 451 (2.9%) episodes of hyperkalemia occurred in 408 patients. In patients with hyperkalemia, chronic kidney disease, hypertension, diabetes, coronary artery disease and heart failure were common comorbidities. Acute kidney injury (AKI) and metabolic acidosis were common metabolic abnormalities, and 359 patients (88%) were on at least one drug associated with hyperkalemia. Mean duration to resolution of hyperkalemia was 12 ±9.9 h. Nonsteroidal anti-inflammatory drugs (HR = 1.59), highest potassium level (HR = 0.61), tissue necrosis (HR = 0.61), metabolic acidosis (HR = 0.77), and AKI (HR = 0.77) were significant independent determinants of duration prior to hyperkalemia resolution. Tissue necrosis (OR = 4.55), potassium supplementation (OR = 5.46), metabolic acidosis (OR = 4.84), use of calcium gluconate for treatment of hyperkalemia (OR = 4.62), AKI (OR = 3.89), and prolonged duration of hyperkalemia (OR = 1.06) were significant independent predictors of in-hospital mortality.ConclusionsTissue necrosis, potassium supplementation, metabolic acidosis, calcium gluconate for treatment of hyperkalemia, AKI and prolonged duration of hyperkalemia are independent predictors of in-hospital mortality.

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We hypothesized that certain subpopulations (elderly and those with greater comorbidity) may not have significant benefit from "fistula first" initiative. A cohort of incident hemodialysis patients from 2005 to 2007, who were ≥70 years old, was derived from the United States Renal Data System. Primary variable of interest was type of vascular access used at first outpatient hemodialysis (i.e., fistula, graft, or central catheter), with primary outcome of all-cause mortality (time to death measured from the first outpatient hemodialysis). A cohort of 82,202 patients was stratified by age (70 to ≤80, 81 to ≤90, and >90). Each group demonstrated a survival benefit with the use of an arterio-venous fistula compared with catheter (hazard ratio [HR] 0.56 [P < 0.001], HR 0.55 [P < 0.001], and HR 0.69 [P = 0.007], respectively). Comparing graft to with a catheter, both groups, 70 to ≤80 and 81 to ≤90, had significant benefit compared with catheter (HR 0.73, P < 0.001 and HR 0.74, P < 0.001, respectively). However, significance was lost in those ≥90 (HR 0.83, P = 0.354). When substratified by comorbidity, those 81 to ≤90 years old with a history of malignancy or peripheral vascular disease also did not reach significant benefit compared with a catheter (HR 0.88, P = 0.423 and HR 0.85, P = 0.221, respectively). While specific subgroups in the hemodialysis population exist where use of fistulas and grafts at time of dialysis initiation is not of proven statistical benefit to survival, elderly hemodialysis patients with comorbidities still appear to benefit from the use of fistulas and grafts.

Objective To evaluate differences in thrombo-inflammatory biomarkers between patients with severe COVID-19 infection/death and mild infection. Patients and Methods Medline, Cochrane Central Register of Controlled Trials, Embase, EBSCO, Web of Science, and CINAHL databases were searched for studies comparing thrombo-inflammatory biomarkers in COVID-19 among severe/non-survivors and non-severe/survivors from January 1, 2020 through July 11, 2020. Inclusion criteria: (1) hospitalized patients ≥18 years comparing severe/non-survivors vs. non-severe/survivors; (2) biomarkers of inflammation and/or thrombosis. A random-effects model was used to estimate the weighted mean difference (WMD) between the two groups of COVID-19 severity. Results Seventy-five studies were included (17,052 patients). Patients with severe COVID-19/non-survivors were older, a greater proportion were men, had a higher prevalence of hypertension, diabetes, cardiac or cerebrovascular disease, chronic kidney disease, malignancy, and COPD. The thrombo-inflammatory biomarkers were significantly higher in patients with severe disease including D-dimer (WMD 0.60, 0.49-0.71, I 2 =83.85%), fibrinogen (WMD 0.42, 0.18-0.67, I 2 =61.88%, p<0.001), CRP (WMD 35.74, 30.16-41.31, I 2 =85.27%), high sensitivity-CRP (WMD 62.68, 45.27-80.09, I 2 =0%), Interleukin-6 (WMD 22.81, 17.90-27.72, I 2 =90.42%) and, ferritin (WMD 506.15, 356.24-656.06, I 2 =52.02%). Moderate to significant heterogeneity was observed for all parameters. Sub-analysis based on disease severity, mortality, and geographic region of studies demonstrated similar inferences. Conclusions Thrombo-inflammatory biomarkers (D-dimer, Fibrinogen, CRP, hs-CRP, ferritin, and IL-6) and marker of end-organ damage (hs-Troponin I) are associated with increased severity and mortality in COVID-19 infection.